Microfabricated micro fluid channels

ABSTRACT

A fluid delivery system including a first substrate having a micro-channel and a well both formed through the first substrate. The fluid delivery system also includes a second substrate and a delivery channel. The second substrate is on the first substrate and the delivery channel is formed between the first and second substrates. The delivery channel provides fluid communication between the micro-channel and the well.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with Government support under Contract NumberDAAD19-00-1-0414 awarded by Army Research Office (ARO), and ContractNumber F49620-01-1-0401 awarded by Air Force Office of ScientificResearch (AFOSR). The Government may have has certain rights in theinvention.

BACKGROUND

This invention relates generally to array chemical transfer devices, andin particular, to a fluid delivery system having an array ofmicro-channels in fluid connection with an array of wells.

In nanolithography, such as dip pen lithography (DPN) or other types ofarrayed chemical transfer methods, it is desirable to provide inks,chemical or biological fluids, to a plurality of probes simultaneously.An arrayed fluid dispensing system with matching spatial configurationto the probe array would allow efficient inking of such an array ofprobes. Neighboring probes with very small distances between them canreceive distinct inks. The probes can then be used to create highdensity arrays of biochemical substances, such as DNA or protein arrays.

BRIEF SUMMARY

According to one aspect of the present invention, a method forfabricating a fluid delivery system is provided. The method includesattaching a first substrate and a second substrate to form a deliverychannel between the first substrate and the second substrate. Thedelivery channel provides fluid communication between a firstmicro-channel and a first well. The first micro-channel and the firstwell are both in the first substrate.

According to another aspect of the present invention, a fluid deliverysystem is provided. The fluid delivery system includes a first substratehaving a micro-channel and a well both formed through the firstsubstrate. The fluid delivery system also includes a second substrateand a delivery channel. The second substrate is on the first substrate,and the delivery channel is formed between the first and secondsubstrates. The delivery channel provides fluid communication betweenthe micro-channel and the well.

According to another aspect of the present invention, a method forforming a micro-pipette is provided. The method includes etching a topsurface of a substrate to remove a portion of the substrate. Thesubstrate has a micro-channel formed through the first substrate, wherethe top surface is opposed to a bottom surface. The top surface, thebottom surface, and the micro-channel are coated with a supportmaterial.

According to another aspect of the present invention, an apparatus fortransferring fluid is provided. The apparatus includes a substratehaving a top surface opposed to a bottom surface and a layer of supportmaterial. The substrate and the layer of support material form amicro-channel. The micro-channel opens at the bottom surface of thesubstrate and extends above the top surface of the substrate.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a cross-sectional view of a fluid delivery systemcontaining multiple substrates, in accordance with one preferredembodiment of the invention;

FIG. 2 illustrates a cross-sectional view of a fluid delivery systemcontaining multiple substrates, in accordance with one preferredembodiment of the invention;

FIG. 3. illustrates an enlarged cross-sectional view of a portion of afluid delivery system containing multiple substrates, in accordance withone preferred embodiment of the invention;

FIG. 4. illustrates a cross-sectional view of a fluid delivery systemcontaining multiple substrates, in accordance with one preferredembodiment of the invention;

FIG. 5. illustrates a cross-sectional view of a fluid delivery systemcontaining multiple substrates, in accordance with one preferredembodiment of the invention; and

FIGS. 6–11 illustrate, in cross-section, process steps for thefabrication of a micro-pipette structure for use in a fluid deliverysystem in accordance with one preferred embodiment of the invention.

It should be appreciated that for simplicity and clarity ofillustration, elements shown in the Figures have not necessarily beendrawn to scale. For example, the dimensions of some of the elements areexaggerated relative to each other for clarity. Further, whereconsidered appropriate, reference numerals have been repeated among theFigures to indicate corresponding elements.

DETAILED DESCRIPTION

The present invention includes micro fluid channels. The micro fluidchannels are formed by etching partially or completely through asubstrate. The micro fluid channels may protrude from the substrate toform micro-pipettes, which may be in the form of an array. The channelsmay be part of a fluid delivery system, including one or more additionalsubstrates, with channels between the substrates connecting the microfluid channel to wells having a larger size, allowing for various fluidsto easily be delivered to the micro fluid channel. These micro fluidchannels may then be used to ink a probe or array of probes, to spotsurfaces. This will allow for patterning, with the various fluids, toform, for example high density arrays of biochemical substances.

A “micro fluid channel” or “micro-channel” means a channel having across-sectional area of at most 10,000 square microns, more preferablyat most 2500 square microns, most preferably at most 100 square microns.

Shown in FIG. 1, in cross-section, is a fluid delivery system 20 whichincludes a first substrate 28 overlying a second substrate 54.Preferably, the first and second substrate 28, 54 comprise a singlecrystal silicon substrate; however, first and second substrate 28, 54may comprise other materials. Preferably, the substrates 28, 54 eachhave a thickness of 1000 to 200 microns, such as 300 to 500 microns.Preferably, the first and second substrates 28, 54 have top surfaces 30,56 which are previously processed and cleaned to remove debris andnative oxides.

First substrate 28 has a top surface 30 opposed to a bottom surface 32.First substrate 28 also has an outer edge 24 surrounding an insidesurface 26, as illustrated in FIG. 1. In one embodiment, the firstsubstrate 28 is formed from a single substrate, as illustrated in FIGS.1 and 4, while in another embodiment, the first substrate 28 is formedfrom multiple substrates, such as an upper substrate 50 and a lowersubstrate 52, and then bonded together, as illustrated in FIGS. 2 and 5.

Upper and lower substrates 50, 52 may be bonded in one of many ways,such as spin on bonding using photoresist or an adhesive polymer foradhesive bonding, which may be patterned (see for example “VOID-FREEFULL WAFER ADHESIVE BONDING” F. Niklaus, et al.); or high-temperaturebonding, for example by heating the substrates together at about 1100°C. Alignment may be achieved using an alignment mark, or using featurespresent on the substrates.

A micro-channel 34 is formed through the first substrate 28 from the topsurface 30 to the bottom surface 32. Preferably, the micro-channel 34 isformed by etching all the way through the first substrate 28 from thetop surface 30 to the bottom surface 32; however other means for formingthe micro-channel 34 may be used, such as drilling. Preferably, themicro-channel 34 is formed using anisotropic etching. In one embodiment,the micro-channel 34 is formed by etching through the top surface 30 toform a first channel 40 and then etching through the bottom surface 32to form a second channel 42, wherein the first and second channels 40,42 are in fluid communication, as illustrated in FIG. 7. Preferably, thecross-sectional area of the first channel 40 is less than thecross-sectional area of the second channel 42. More preferably, theratio of the cross-sectional area of the first channel 40 to thecross-sectional area of the second channel 42 is between 1 to 1 and 1 to10.

The micro-channel 34 has an inlet 38 for receiving fluid 22 from adelivery channel 66 and an outlet 36 for delivering fluid 22,preferably, to a probe 78, as illustrated in FIG. 3. In one embodiment,the outlet 36 has a cross-sectional area that is generally circular inshape. Preferably, the outlet 36 has a cross sectional area that is atmost 10,000 square microns, more preferably at most 2,500 squaremicrons, and most preferably at most 100 square microns. In oneembodiment, the outlet 36 has a cross sectional area that is between tenand 10,000 square microns. Preferably, the inlet 38 has across-sectional area that is larger than the cross-sectional area of theoutlet 36. The cross-sectional areas and shapes of the inlet 38 and theoutlet 36 may be freely chosen, using patterning techniques, such asthose used to pattern semiconductor substrates.

Preferably, the first substrate 28 includes a hydrophobic surface 74surrounding the outlet 36, as illustrated in FIG. 1. The hydrophobicsurface 74 prevents fluid 22 from overflowing and unintentionallyexiting the outlet 36, and possibly causing cross-contamination betweenfluids 22. The hydrophobic surface 74 can be formed in one of many ways,such as coating the outlet 36 of the micro-channel 34 with a hydrophobicmaterial, for example a silane or thiol, such as 1-octadecanethiol(ODT), or a photoresist. Preferably, an array of micro-channels 34 isformed through the first substrate 28 from the top surface 30 to thebottom surface 32, as illustrated in FIG. 1. The distance D₁ betweenadjacent micro-channels 34 is preferably at most 1000 microns, morepreferably at most 600 microns, most preferably at most 200 microns.

A well 44 is formed through the first substrate 28 from the top surface30 to the bottom surface 32. Preferably, the well 44 is formed byetching all the way through the first substrate 28 from the top surface30 to the bottom surface 32; however other means for forming the well 44may be used, such as drilling. Preferably, the well 44 is formed usingreactive ion etching. The well 44 has an inlet 46 for receiving fluid 22from a fluid delivery device, such as a conventional pipette or pump.The well 44 also includes a well outlet 48 for delivering fluid 22 tothe delivery channel 66, as illustrated in FIG. 1. In one embodiment,the well inlet 46 has a cross-sectional area that is generally circularin shape. Preferably, the well inlet 46 has a cross-sectional area thatis greater than the cross-sectional area of the micro-channel outlet 36.Forming the well inlet 46 with a cross-sectional area that is largerthan the cross-sectional area of the micro-channel outlet 36 allows forfluids 22 to be easily injected into the well inlet 46, and yet still bedeliverable, through the smaller micro-channel outlet 36, to a probe 78.Preferably, the well inlet 46 has a cross sectional area that is between1 and 20 square millimeters, more preferably between 3 and 12 squaremillimeters, and most preferably between 5 and 10 square millimeters. Inone embodiment, the distance D₃ between adjacent wells 44 is greaterthan the distance D₁ between adjacent micro-channels 34 or the distanceD₂ between adjacent micro-pipettes 84, as illustrated in FIGS. 1 and 2.

Preferably, the array of wells 44 is formed through the first substrate28 from the top surface 30 to the bottom surface 32, as illustrated inFIG. 1. Preferably, the array of wells 44 is formed near the outer edge24 of the first substrate 28, while the array of micro-channels 34 isformed at the inside surface 26 of the first substrate 28, asillustrated in FIG. 1.

Second substrate 54 has a top surface 56 opposed to a bottom surface 58.Second substrate 54 also has an outer edge 62 surrounding an insidesurface 64, as illustrated in FIG. 1. Second substrate 54 is positionedso that the top surface 56 is on the bottom surface 32 of the firstsubstrate 28. In one embodiment, an extended channel 60 is formedthrough the second substrate 54 from the top surface 56 to the bottomsurface 58. Preferably, the extended channel 60 is formed by etching allthe way through the second substrate 54 from the top surface 56 to thebottom surface 58; however, other means for forming the extended channel60 may be used, such as drilling. Preferably, the extended channel 60 isformed using reactive ion etching. The extended channel 60 has an inlet61 for receiving fluid 22 from a secondary delivery channel 67 and anoutlet 63 for delivering fluid 22 to the inlet 38 of the micro-channel34, as illustrated in FIGS. 1 and 3. The secondary delivery channel 67is formed between the second substrate 54 and a third substrate 82, asillustrated in FIG. 1. In one embodiment, the outlet 63 has across-sectional area that is generally circular in shape.

The delivery channel 66 is formed between the first and secondsubstrates 28, 54, as illustrated in FIGS. 1 and 2. Preferably, theheight H of the delivery channel, as illustrated in FIG. 3, is betweenone and twenty microns, and more preferably, at most ten microns. Thedelivery channel 66 may be formed in one of many ways. In oneembodiment, the delivery channel 66 includes a groove 210 that is formedon the top surface 56 of the second substrate 54. In one embodiment, thedelivery channel 66 includes a groove 130 that is formed on the bottomsurface 32 of the first substrate 28. In one embodiment, the deliverychannel 66 includes a first groove that is formed on the top surface 56of the second substrate 54 and a second groove that is formed on thebottom surface 32 of the first substrate 28. The first substrate 28 isaligned with the second substrate 54 50 that the delivery channel 66allows for fluid to travel between the micro-channel 34 and the well 44.The delivery channel 66 includes an inlet 70 for receiving fluid and anoutlet 68 for delivering fluid 22. The delivery channel inlet 70receives fluid 22 from the well outlet 48 of the well 44, while thedelivery channel outlet 68 delivers fluid 22 to the inlet 38 of themicro-channel 34. The delivery channel inlet 70 is adjacent to the welloutlet 48, and the delivery channel outlet 68 is adjacent to the inlet38, as illustrated in FIG. 1.

In one embodiment, the micro-channel 34 extends both above and below thetop surface 30 of the first substrate 28, as illustrated in FIGS. 2–5.In this embodiment, the micro-channel 34 may be formed entirely from thefirst substrate 28, a portion of the micro-channel 34 may be formed fromthe first substrate 28, or the micro-channel 34 may be formed from asecond material. The second material may be any material that can beformed or coated onto a surface, such as those used in semiconductorprocessing. Examples include oxides, such as silicon oxide and siliconoxynitride, nitrides such as silicon nitride and titanium nitride,metals such as tungsten and gold, and polymers. Preferably, themicro-channel 34 is formed from the second material, wherein the secondmaterial extends both above and below the top surface 30 of the firstsubstrate 28.

In one embodiment, a method for fabricating the fluid delivery system 20is disclosed. Referring to FIG. 1 the fluid delivery system 20 isfabricated by attaching the first substrate 28 and the second substrate54 to form the delivery channel 66, wherein the delivery channel 66provides fluid communication between the micro-channel 34 and the well44. Preferably, the first substrate 28 is aligned with the secondsubstrate 54 so that the inlet 70 of the delivery channel 66 is adjacentthe outlet 48 of the well 44, while the outlet 68 of the deliverychannel 66 is adjacent the inlet 38 of the micro-channel 34. In thisway, the micro-channel 34 is in fluid connection with the well 44, andthus fluid 22 may travel from the inlet 46 of the well 44 through thewell 44, the delivery channel 66, and the micro-channel 34, only to exitat the outlet 36 of the micro-channel 34. Preferably, either alignmentmarks or existing features on one or both of the first and secondsubstrates 28, 54 are used to align the first substrate 28 with thesecond substrate 54.

Once the delivery channel 66 is formed, the fluid 22 is delivered to thewell 44. The fluid 22 travels down the well 44, through the deliverychannel 66, and up the micro-channel 34 to the outlet 36. Fluid 22 canbe forced up into the micro-channel 34 by pumping the fluid 22 throughthe well 44 and the delivery channel 66. Fluid 22 may be pumped throughthe well 44 and the delivery channel 66 using a variety of techniques,such as by creating a pressure differential between the inlet 46 and theoutlet 36, or simply by capillary action. Preferably, the fluid 22 iskept in the micro-channel 34 and prevented from unintentionally exitingthe micro-channel 34 by creating a hydrophobic surface 74 adjacent theoutlet 36 of the micro-channel 34. Once the micro-channel 34 is filledwith fluid 22, the fluid 22 can then be transferred to a probe 78, suchas an SPM (Scanning Probe Microscopy) probe, and more specifically tothe tip 80 of the probe 78, as illustrated in FIG. 3.

In one embodiment, a micro-pipette 84 forms the micro-channel 34.Preferably, a portion of the micro-pipette 84 extends both above andbelow the top surface 30 of the first substrate 28, as illustrated inFIG. 2. Preferably, the fluid delivery system 20 includes an array ofmicro-pipettes 84, as illustrated in FIGS. 2–5, allowing for multiplefluids 22 to be dispensed from the array of micro-channels 34.

In one embodiment, a method for fabricating the micro-pipette 84 isdisclosed, as illustrated in FIGS. 6–11. Referring to FIG. 6, asubstrate 88, such as first substrate 28, is provided. Preferably, thesubstrate 88 has a top surface 90 which is previously processed andcleaned to remove debris and native oxides. The top surface 90 isopposed to a bottom surface 92. Preferably, the bottom surface 92 isalso previously processed and cleaned to remove debris and nativeoxides.

Referring to FIG. 7, a channel 94, such as a micro-channel 34, having awall 95 is formed through the substrate 88 from the top surface 90 tothe bottom surface 92. Preferably, the channel 94 is formed by etchingall the way through the substrate 88 from the top surface 90 to thebottom surface 92; however, other means for forming the channel 94 maybe used, such as drilling. Preferably, the channel 94 is formed usingreactive ion etching. In one embodiment, the channel 94 is formed byetching through the top surface 92 to form a first channel 100 and thenetching through the bottom surface 92 to form a second channel 102,wherein the first and second channels 100, 102 connect, as illustratedin FIG. 7. The channel 94 has an inlet 98 for receiving fluid, such asfluid 22, and an outlet 96 for delivering fluid to, for example, aprobe, such as probe 78. In one embodiment, the outlet 96 has across-sectional area that is generally circular in shape. In yet anotherembodiment, the inlet 98 has a cross-sectional area that is larger thanthe cross-sectional area of the outlet 96. The cross-sectional areas andshapes of the inlet 98 and the outlet 96 may be freely chosen, usingpatterning techniques, such as those used to pattern semiconductorsubstrates.

After forming the channel 94, the top surface 90, the bottom surface 92,and the wall 95 of the channel 94 are all coated with a layer 76 ofsupport material, as illustrated in FIG. 8. The support material mayinclude any material that can be formed or coated onto a surface, suchas those used in semiconductor processing. Examples include oxides, suchas silicon oxide and silicon oxynitride, nitrides such as siliconnitride and titanium nitride, metals such as tungsten and gold, andpolymers. The support material may be formed by chemical reaction withthe substrate 88, for example by oxidation, or by coating, for examplewith chemical vapor deposition or oblique angle physical vapordeposition. Preferably, the support material is different from thematerial contained in the substrate 88. Multiple materials may also beused, and these may be applied with the first support material, or theymay be applied after further processing steps. In one embodiment, thelayer 76 is silicon dioxide which is formed by reacting the substrate90, preferably made of silicon, with oxygen.

After forming the layer 76, a portion of the layer 76 is removed.Preferably, the layer 76 is removed from the top surface 90 to exposethe top surface 90 of the substrate 88. In one embodiment, the layer 76is removed from the bottom surface 92 to expose the bottom surface 92 ofthe substrate 88. Layer 76 may be removed in one of a number of ways,such as the use of chemical-mechanical polishing or etching. The channel94 may be filled with a protectant, such as wax, to avoid damaging thechannel 94 with a polishing agent. The protectant may be removed with asolvent, such as acetone.

Upon removing the layer 76, the substrate 88 is then etched to remove aportion of either the top surface 90 or the bottom surface 92 of thesubstrate 88, as illustrated in FIG. 10. Preferably, the substrate 88 isetched to a depth D₄, as illustrated in FIG. 10, of between 50 and 500microns, and more preferably, a depth of at most 150 microns. Varioustypes of etching may be used to remove a portion of the substrate 88,such as wet etching with ethylene diamine pyrocatechol or potassiumhydroxide, or dry etching. Preferably, the top surface 90 is etched toremove a portion of the substrate 88 and create an etched surface 91which is closer to the bottom surface 92 than the original top surface90.

Preferably, upon etching the substrate 88, a hydrophobic material isapplied to the surface 106 surrounding the outlet 96 to create ahydrophobic surface 108, as illustrated in FIG. 11.

The individual processing steps used in accordance with the presentinvention are well known to those of ordinary skill in the art, and arealso described in numerous publications and treatises, including:Encyclopedia of Chemical Technology, Volume 14 (Kirk-Othmer, 1995, pp.677–709); Semiconductor Device Fundamentals by Robert F. Pierret(Addison-Wesley, 1996); Silicon Processing for the VLSI Era by Wolf(Lattice Press, 1986, 1990, 1995, vols 1–3, respectively); and MicrochipFabrication: A Practical Guide to Semiconductor Processing by Peter VanZant (4^(th) Edition, McGraw-Hill, 2000). In order to etch through thesubstrate, techniques such as deep ion etching may be used (also knownas the Bosch process).

The fluid delivery system may be used to form patterns using fluids onsurfaces. For example, if the fluid is an ink, then a surface, such aspaper, could be printed with the probes after they have received theink, to form microprinting. Biological arrays may similarly be formed,for example by using fluids containing biological compounds, such asnucleotides (RNA, DNA, or PNA), proteins (enzymes, antibodies, etc.),lipids, carbohydrates, etc. to spot a substrate, such as glass, silicon,or polymers. Since each micro-channel may be supplied for a dedicatedwell, very complex arrays may be produced quickly.

Numerous additional variations in the presently preferred embodimentsillustrated herein will be determined by one of ordinary skill in theart, and remain within the scope of the appended claims and theirequivalents. For example, while the examples provided above relate tosilicon-based semiconductor substrates, it is contemplated thatalternative semiconductor materials can likewise be employed inaccordance with the present invention, and that the semiconductorsubstrates may be undoped, P-doped, or N-doped. Suitable materials forthe substrates include but are not limited to silicon, gallium arsenide,germanium, gallium nitride, aluminum phosphide, Si_(1−x)Ge_(x) andAl_(x)Ga_(1−x)As alloys, wherein x is greater than or equal to zero andless than or equal to one, the like, and combinations thereof.Additional examples of materials for use in accordance with the presentinvention are set forth in Semiconductor Device Fundamentals by RobertF. Pierret (p. 4, Table 1.1, Addison-Wesley, 1996).

Although the invention has been described and illustrated with referenceto specific illustrative embodiments thereof, it is not intended thatthe invention be limited to those illustrative embodiments. Thoseskilled in the art will recognize that variations and modifications canbe made without departing from the spirit of the invention.

The invention claimed is:
 1. A fluid delivery system, comprising: afirst substrate comprising: a first micro-channel comprising a firstmicro-channel outlet, a first well, a second micro-channel comprising asecond micro-channel outlet, and a second well, each formed through thefirst substrate; a second substrate on the first substrate; a firstdelivery channel formed between the first and the second substrates, thefirst delivery channel establishing fluid communication between thefirst micro-channel and the first well; and a second delivery channelestablishing fluid communication between the second micro-channel andthe second well; and a scanning probe microscopy probe for receivingfluid from the micro-channels, wherein the probe is moveable to and fromthe micro-channel outlets, where the first and second micro-channeloutlets are separated by at most 1000 microns.
 2. The system of claim 1,wherein at least one of the delivery channels comprises a groove formedon a surface of the second substrate.
 3. The system of claim 1, whereeach of the wells has an inlet for receiving fluid, each of themicro-channels has an outlet for delivering fluid, and a cross-sectionalarea of at least one of the well inlets is greater than a crosssectional area of at least one of the micro-channel outlets.
 4. Thesystem of claim 3, wherein the cross sectional area of each of the wellinlets is between one and twenty square millimeters, and the crosssectional area of each of the micro-channel outlets is between ten and10,000 square microns.
 5. The system of claim 3, further comprising ahydrophobic surface surrounding each of the micro-channel outlets. 6.The system of claim 3, wherein each of the micro-channel extends aboveand below a surface of the first substrate.
 7. The system of claim 3,wherein the first substrate comprises a plurality of substrates.
 8. Thesystem of claim 1, further comprising a third substrate on the secondsubstrate.
 9. The system of claim 8, the second substrate furthercomprising an extended channel establishing fluid communication betweenthe second micro-channel and the second delivery channel, the extendedchannel formed through the second substrate; and the second deliverychannel formed between the second and the third substrates.
 10. Thesystem of claim 1, where at least one delivery channel comprises agroove formed on a surface of the first substrate.
 11. The system ofclaim 1, where the first substrate has a thickness of at most 500microns.
 12. The system of claim 1, where the first substrate is bondedto the second substrate by spin-on bonding or high temperature bonding.13. The system of claim 1, where the first and second micro-channelsform a micro-pipette.
 14. The system of claim 1, where themicro-channels are formed by reactive ion etching.
 15. The system ofclaim 14, where the micro-channels are formed by a first etch on a topsurface of the first substrate and a second etch on a bottom surface ofthe first substrate.
 16. The system of claim 15, where the first etchforms a first micro-channel width and the second etch forms a secondmicro-channel width, the first micro-channel width in fluidcommunication with the second micro-channel width.
 17. The system ofclaim 1, where the distance between the first and second wells isgreater than the distance between the first and second micro-channels.